DrugindexOnline^{2nd edition}

Pronouncation: (VAL-ay-SYE-kloe-vir hye-droe-KLOR-ide)
Class: Antiherpes virus agent

Trade Names:
Valtrex
- Tablets 500 mg
- Tablets 1 g

Mechanism of Action

Pharmacology

Converted to acyclovir, which then inhibits viral DNA replication by interfering with viral DNA polymerase.

Pharmacokinetics

Absorption

Rapidly absorbed from the GI tract. Bioavailability is about 55%. C _max is less than 0.5 mcg/mL.

Distribution

Protein binding ranges from 14% to 18%.

Metabolism

Converted to acyclovir and/or L-valine by first-pass intestinal or hepatic metabolism.

Elimination

About 46% is recovered in urine. About 47% is recovered in feces.

Special Populations

Renal Function Impairment

Dose reduction is recommended.

Elderly

Dose modification may be necessary in elderly patients with reduced renal function.

Indications and Usage

Treatment of herpes zoster (shingles); treatment or suppression of genital herpes; treatment of herpes labialis (cold sores).

Contraindications

Hypersensitivity or intolerance to valacyclovir, acyclovir, or any component of the formulation.

Dosage and Administration

Herpes zoster
Adults

PO 1 g tid for 7 days (initiate therapy within 48 hr of onset of rash).

Genital Herpes
Adults Initial Episodes

PO 1 g bid for 10 days (initiate therapy within 48 to 72 hr of onset of signs and symptoms).

Recurrent Episodes

PO 500 mg bid for 3 days (initiate therapy within 24 hr of onset of signs or symptoms).

Suppressive Therapy

PO 1 g once daily. In patients with a history of 9 or fewer recurrences/yr, 500 mg/day may be administered.

HIV-Infected Patients
Adults

PO 500 mg bid for suppressive therapy in HIV-infected patients with CD4 cell count of at least 100 cells/mm ³ (efficacy beyond 6 mo of therapy has not been established).

Herpes Labialis
Adults

PO 2 g bid for 1 day approximately 12 hr apart, initiated at earliest symptoms of cold sore (eg, tingling, burning, itching).

Acute or Chronic Renal Impairment
Adults

PO

• Herpes Zoster: Ccr 30 to 49 mL/min, give 1 g every 12 hr; Ccr 10 to 29 mL/min, give 1 g every 24 hr; Ccr less than 10 mL/min, give 500 mg every 24 hr.
• Genital herpes (initial treatment): Ccr 10 to 29 mL/min, give 1 g every 24 hr; Ccr less than 10 mL/min, give 500 mg every 24 hr.
• Genital herpes (recurrent episodes): Ccr 29 mL/min or less, give 500 mg every 24 hr.
• Genital herpes (suppressive therapy): Ccr 29 mL/min or less, give 500 mg every 24 hr. In patients with a history of 9 or fewer recurrences/yr and Ccr 29 mL/min or less, give 500 mg every 48 hr.
• Genital herpes suppressive therapy in HIV-infected patients: Ccr 29 mL/min or less, give 500 mg every 24 hr.
• Herpes labialis (do not exceed 1 day of treatment): Ccr 30 to 49 mL/min, give two 1 g doses about 12 hr apart; Ccr 10 to 29 mL/min, give two 500 mg doses about 12 hr apart; Ccr less than 10 mL/min, give 500 mg as a single dose.

Storage/Stability

Store at controlled room temperature (59° to 77°F).

Drug Interactions

Cimetidine, probenecid

Increased acyclovir serum concentrations.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension, tachycardia (postmarketing).

CNS

Headache (38%); depression (7%); dizziness (4%); aggressive behavior, agitation, ataxia, coma, confusion, decreased consciousness, dysarthria, encephalopathy, mania, psychosis (including audio and visual hallucinations), seizures, tremors (postmarketing).

Dermatologic

Alopecia, erythema multiforme, rashes (including photosensitivity) (postmarketing).

EENT

Visual abnormalities (postmarketing).

GI

Nausea (15%); abdominal pain (11%); vomiting (6%); diarrhea (postmarketing).

Genitourinary

Dysmenorrhea (8%); renal failure (postmarketing).

Hematologic-Lymphatic

Aplastic anemia, leukocytoclastic vasculitis, thrombocytopenia (postmarketing).

Hepatic

Hepatitis (postmarketing).

Lab Tests

Increased AST (4%); decreased hemoglobin, increased serum creatinine, leukopenia (1%); abnormal liver enzymes, elevated creatinine (postmarketing).

Miscellaneous

Arthralgia (6%); acute hypersensitivity reactions (including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria), facial edema (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Undetermined (acyclovir is excreted in breast milk).

Children

Safety and efficacy not established.

Elderly

Dosage reduction may be necessary, depending on underlying renal status.

Renal Function

Dosage reduction is recommended; exercise caution when giving valacyclovir to patients with renal function impairment or those receiving potentially nephrotoxic drugs.

Immunocompromised

Safety and efficacy not established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome

May occur and has resulted in death in patients with advanced HIV disease and also in allogenic bone marrow and renal transplant recipients receiving valacyclovir 8 g/day.

Overdosage

Symptoms

Acute renal failure, anuria.

Patient Information

• Explain name, dose, action, and potential adverse reactions of drug.
• Obtain patient history, including drug history and any known allergies.
• Review dose and appropriate dosing schedule depending on condition being treated (shingles, cold sores, or genital herpes). Instruct patient to take medication exactly as prescribed and not to stop taking or change the dose unless advised by health care provider.
• Advise patient that medication can be taken without regard to meals but to take with food if stomach upset occurs.
• Remind patient using medication for cold sores that it is not a cure and to initiate therapy at the first symptom of a cold sore (eg, tingling, itching, burning). Remind patient that treatment should not exceed 2 doses taken about 12 hr apart.
• Remind patient using medication for recurrent episodes of genital herpes to initiate therapy at the first sign or symptom or recurrence and that medication may not be effective if started more than 24 hr after onset of signs or symptoms of recurrence.
• Inform patient that there are no data on treatment of herpes zoster when initiated more than 72 hr after the onset of the zoster rash.
• Advise patient with genital herpes that this drug is not a cure for genital herpes and does not prevent transmission of virus. Instruct patient to avoid sexual intercourse when lesions and/or symptoms are present to avoid infecting partner.
• Advise patient to contact health care provider if medication does not seem to be controlling lesions and/or symptoms or if intolerable side effects develop.
• Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing until tolerance is determined.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.
• Instruct patient not to take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
• Advise patient that follow-up visits may be necessary to monitor therapy and to keep appointments.